PD‐1 Blockade Cellular Vesicles for Cancer Immunotherapy
Year: 2018
Type: article
Abstract: Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD‐L1 that exhausts antigen‐specific CD8 + T cells through PD‐1 receptors. Checkpoint blockade antibodies against PD‐1 or PD‐L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD‐1 receptors on their membranes, which enhance antitumor responses by disrupting the PD‐1/PD‐L1 immune inhibitory axis, are reported. PD‐1 NVs exhibit a long circulation and can bind to the PD‐L1 on melanoma cancer cells. Furthermore, 1‐methyl‐tryptophan, an inhibitor of indoleamine 2,3‐dioxygenase can be loaded into the PD‐1 NVs to synergistically disrupt another immune tolerance pathway in the tumor microenvironment. Additionally, PD‐1 NVs remarkably increase the density of CD8 + tumor infiltrating lymphocytes in the tumor margin, which directly drive tumor regression.
Source: Advanced Materials
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Alfred P. Sloan Foundation, University of North Carolina, North Carolina State University, Georgia Clinical and Translational Science Alliance, National Natural Science Foundation of China, China Postdoctoral Science Foundation, National Institutes of Health, University of North Carolina at Chapel Hill, Fok Ying Tong Education Foundation, North Carolina Translational and Clinical Sciences Institute, University of North Carolina at Chapel Hill
OpenAlex ID: W2799662486